Protein serine/threonine phosphatases (PSPs) play a critical role in intracellular signaling processes and are sensitive to a diverse set of natural products.1 Examples of small molecules displaying inhibitory activity against class 1, 2A, or 2B protein phosphatases (PPs) include okadaic acid,1 2 the microcystins,3 calyculin A,4 nodularin,5 tautomycin,6 and cantharidine,7 as well as the complexes of FK506 and cyclosporin A with their cognate immunophilins.8 Recently, enzyme assay-guided screening and fractionation of crude extracts from the marine sponge Theonella swinhoei Gray led to the isolation of the extremely potent PP-1 inhibitor motuporin (l).9 10*Motuporin (Figure 1) is a cyclic pentapeptide that belongs to a family of structurally related toxins, including the microcystins and nodularin (2), that are characterized by the hallmark C20 amino acid (25,35,85,95)-3amino-9-methoxy-2,6,8-trimethyl-10-phenyl-4,6-decadienoic acid

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The class I major histocompatibility complex (MHC) glycoprotein HLA-B27 binds short peptides containing arginine at peptide position 2 (P2). The HLA-B27/peptide complex is recognized by T cells both as part of the development of the repertoire of T cells in the cellular immune system and during activation of cytotoxic T cells. Based on the three-dimensional structure of HLA-B27, we have synthesized a ligand with an aziridine-containing side chain designed to mimic arginine and to bind covalently in the arginine-specific P2 pocket of HLA-B27. Using tryptic digestion followed by mass spectrometry and amino acid sequencing, the aziridinecontaining ligand is shown to alkylate specifically cysteine 67 of HLA-B27. Neither free cysteine in solution nor an exposed cysteine on a class II MHC molecule can be alkylated, showing that specific recognition between the anchor side-chain pocket of an MHC class I protein and the designed ligand (propinquity) is necessary to induce the selective covalent reaction with the MHC class I molecule.Cytotoxic T-lymphocytes recognize antigens as short peptides bound to major histocompatibility complex (MHC) class I molecules that consist of a heavy chain and f32-microglobulin (f32m) (reviewed in ref.

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Following a known synthetic procedure, the porphyrin‐cyclophane 1 having a porphyrin attached by two straps to an apolar cyclophane binding site was prepared. Upon metallation, the ZnII and FeIII derivatives 2 and 3, respectively, were obtained in good yields. Treatment of 3 with base yielded the μ‐oxo dimer 4 in which the two oxo‐bridged porphyrins moieties are both capped by cyclophane binding sites. All compounds 1–4 are freely soluble in protic solvents such as MeOH and CF3CH2OH, and the FeIII derivatives 3 and 4 are active cytochrome P‐450 mimics in these protic environments. Strong inclusion complexation of polycyclic aromatic hydrocarbons by 1 and 3 in alcoholic solvents was observed and quantified by 1H‐NMR and UV/VIS titrations. Acenaphthylene binds in an ‘equatorial’ orientation which locates its reactive 1,2‐double bond near the porphyrin center, whereas phenanthrene binds ‘axially’ with the reactive 9,10‐double bond oriented away from the porphyrin. The reduction potential of 3 was not significantly altered by substrate binding. In the unbound form, the FeIII center in porphyrin 3 was found by ESR and 1H‐NMR to prefer a high‐spin state (S = 5.2). In CF3CH2OH, using iodosylbenzene as O‐transfer agent, the FeIII derivative 3 catalyzed the oxidation of acenaphthylene to acenaphthen‐1‐one (14). Phenanthrene inhibited the reaction, possibly as a result of strong but nonproductive binding. Under similar conditions, isotetralin (18) was aromatized with high turnover to 1,4‐dihydronaphthalene. The μ‐oxo dimer 4 also showed high activity in the oxidation of acenaphthylen in MeOH, a result which provides strong evidence for efficent supramolecular catalysis. Due to as yet unknown reaction channels leading to polymeric products, poor mass balances were generally obtained in the oxidations effected in MeOH and CF3CH2OH in the presence of PhIO.